DEVELOPMENTAL-CHANGES AND DIFFERENTIAL REGULATION BY TESTOSTERONE ANDESTRADIOL OF GROWTH-HORMONE RECEPTOR EXPRESSION IN THE RABBIT

To investigate the effects of testosterone and estradiol (E(2)) on gro wth hormone receptor (GH-R) gene expression, we measured GH-R mRNA lev els in relation to the changes of sex steroid concentrations in the no rmal male rabbits aged 1-12 months and after administration of testost erone or E(2) to castrated male rabbits. In the normal animals, E(2) l evels were below the detection limit in all age groups, and testostero ne levels were below the detection limit at 1 month, increased at 2 mo nths and reached the plateau of the adult levels after 4 months. Liner GH-R mRNA levels were low at 1 month, reached a peak at 2 months and then decreased slightly thereafter. In the castrated animals, liner an d growth plate GH-R mRNA levels were increased in the testosterone-tre ated group (162.0 +/- 12.0%, p < 0.025; 128.4 +/- 7.6%; p < 0.025) and reduced in the E(2)-treated group (29.6 +/- 6.2%, p < 0.005; 53.6 +/- 11.3%, p < 0.025). Sex steroid administration did not result in any s ignificant change in GH-R mRNA levels in striated muscle, kidney and h eart. Serum GH concentrations were increased in E(2) (15.3 +/- 7.7 mu g/l vs 4.8 +/- 2.2 mu g/l, p < 0.025) but the increase was not signifi cant in testosterone-treated animals (8.4 +/- 7.7 mu g/l vs 4.8 +/- 2. 2 mu g/l). Both testosterone and E(2) treatment resulted in a reductio n of mean serum growth hormone-binding protein (GHBP) levels compared to control animals (1077 +/- 422 pmol/l, p < 0.01; 1137 +/- 443 pmol/l , p < 0.01; 2308 +/- 565 pmol/l). We conclude that in addition to thei r stimulatory effect on GK secretion, testosterone and E(2) have oppos ite effects on GH-R gene expression in liver and growth plate in the r abbit. The modulation of GH-R expression by sex steroids may be import ant for growth during sexual maturation in mammals.